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Abstract
LHF-535 is a small molecule antiviral currently in development for the treatment of Lassa fever, a zoonotic disease endemic in West Africa that generates significant morbidity and mortality. Current treatment options are inadequate, and there are no approved therapeutics or vaccines for Lassa fever. LHF-535 was evaluated in a lethal guinea pig model of Lassa pathogenesis, using once-daily administration of a fixed dose (50 mg/kg/day) initiating either 1 or 3 days after inoculation with a lethal dose of Lassa virus. LHF-535 reduced viremia and clinical signs and protected all animals from lethality. A subset of surviving animals was rechallenged four months later with a second lethal challenge of Lassa virus and were found to be protected from disease. LHF-535 pharmacokinetics at the protective dose in guinea pigs showed plasma concentrations well within the range observed in clinical trials in healthy volunteers, supporting the continued development of LHF-535 as a Lassa therapeutic.
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1 U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Virology Division, Frederick, USA (GRID:grid.416900.a) (ISNI:0000 0001 0666 4455)
2 Kineta, Inc., Seattle, USA (GRID:grid.429501.b); AltPep, Seattle, USA (GRID:grid.429501.b)
3 Kineta, Inc., Seattle, USA (GRID:grid.429501.b); Lyell Immunopharma, Seattle, USA (GRID:grid.510010.5)
4 Kineta, Inc., Seattle, USA (GRID:grid.429501.b)
5 Kineta, Inc., Seattle, USA (GRID:grid.429501.b); Sutro Biopharma, South San Francisco, USA (GRID:grid.510077.4) (ISNI:0000 0004 1799 1576)